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  • Jia-jia WANG, Zhi-jun YANG, Xiu-juan YANG, Peng-xian NIU, Shuo LI, Guo-jian DUAN, Yi-hong TIAN, Qing-yun JI
    Acta Pharmaceutica Sinica. 2025, 60(3): 679-692.

    Transient receptor potential vanilloid (TRPV), an important class of non-selective cation channels, is closely associated with a variety of physiological and pathological processes. Pungent flavour is one of the important flavours in the doctrine of five flavours in traditional Chinese medicine, which has the functions of relieving the epidermis, moving the Qi, activating the blood and so on, which has a variety of main treatments. Modern research has shown that the active ingredients in numerous pungent Chinese medicine have the ability to modulate TRPV channels. The purpose of paper is to explore the biological characteristics of TRPV channels, the modern research process of pungent Chinese medicine and its mechanism in inflammation, pain and other pathological processes. This paper discusses the research progress of the pharmacological action of pungent Chinese medicine based on TRPV channel, in order to reveal the scientific connotation of spicy traditional Chinese medicine, and also provide new research ideas and models for the modern research of Chinese medicine.

  • Hua-miao WANG, Chun-ze ZHANG
    Acta Pharmaceutica Sinica. 2025, 60(3): 693-699.

    Colorectal cancer (CRC), a prevalent and deadly digestive malignancy, primarily causes death through recurrence and metastasis. Current treatments include surgery, radiotherapy, chemotherapy, and immunotherapy, but they have significant side effects and high recurrence rates. Research shows traditional Chinese medicine (TCM) can alleviate symptoms, reduce adverse reactions, enhance quality of life, prevent recurrence and metastasis post-surgery, and improve survival rates. This review explores TCM's theoretical framework, advantages in CRC management, and potential in modulating intestinal flora for CRC prevention and treatment.

  • Yu-xin ZHANG, Yu CHEN, Feng ZHANG, Yao-yang LIU, Fang FAN, Xiao-fei CHEN
    Acta Pharmaceutica Sinica. 2025, 60(3): 762-770.

    In this thesis, we propose to establish a phage display method for screening adalimumab (ADM)-specific binding peptide to provide a particular element of recognition for clinical studies of ADM, and to successfully establish an indirect enzyme-linked immunosorbent assay (i-ELISA) based on this peptide for clinical detection of ADM. With ADM as the target molecule, five rounds of peptide elution were performed using phage display technology by putting it into the M13 linear dodecapeptide library. By measuring the titer of each round of eluate, it was found that the recovery rate increased from 7.28×10-6 to 1.55×10-3, indicating that the peptides binding to ADM in the eluate were continuously enriched, and the enrichment effect was better; the fifth round of screening amplicons were sequenced, and it was found that five peptide sequences appeared with high frequency, which were considered to be potentially able to bind specifically to ADM and were synthesised; the specific binding ability of the five peptide sequences to ADM was verified and identified by surface plasmon resonance (SPR) and ELISA experiments, respectively, and the results showed that the first peptide sequence (Pep1) and the second peptide sequence (Pep2) showed specific binding to ADM, with the affinity constants (KD) of 7.91×10-5 mol·L-1 and 1.67×10-5 mol·L-1, respectively, and of which the affinity constant of Pep1 with ADM isotype antibody IgG was 1.35×10-4 mol·L-1, which was one order of magnitude lower than that with ADM, and thus Pep1 was determined to be a specific binding peptide for ADM. Based on Pep1, an indirect ELISA method for the analysis of the antibody-drug ADM was successfully established. With the increasing concentration of ADM the OD450 value showed a regular change, and the method can be used for clinical ADM blood concentration monitoring. In this study, we obtained a peptide that can specifically bind to ADM, and this peptide sequence can be used as a specific recognition element for ADM, which not only enables the monitoring of ADM blood concentration, but also provides an effective tool for the accurate qualitative and quantitative quantification of ADM in vivo and ex vivo, and at the same time provides a new strategy and idea for the discovery of recognition elements of other monoclonal antibody drugs.

  • Bai-hao LAO, Jian SUN, Jing-xian ZHANG, Hong YU, Ying-ying RAN, Fan HUANG, Shen JI, Qing HU
    Acta Pharmaceutica Sinica. 2025, 60(3): 791-800.

    A detection method using UHPLC-MS/MS was established for the determination of 53 prohibited veterinary drug residues in goat horns, including 16 tranquilizers, 14 β-agonists, chloramphenicol, 4 fluoroquinolones, 7 nitroimidazoles, 3 quinoxalines, and 8 other compounds. Samples were extracted using salting-out assisted liquid-liquid extraction (SALLE). A Zorbax Eclipse Plus C18 column (1.8 μm, 3.0 mm × 150 mm, Agilent) was used with 0.1% formic acid solution-acetonitrile as the mobile phase for gradient elution. Detection was performed in positive and negative electrospray ionization modes using multiple reaction monitoring (MRM). All 53 analytes showed good linearity within their respective concentration ranges, with correlation coefficients above 0.99. The average recoveries at three spiked levels ranged from 70.4% to 118.7%, with relative standard deviations (RSDs) ranging from 0.69% to 12.07%. The limits of detection (LODs) ranged from 0.1 to 50 μg·kg-1, and the limits of quantitation (LOQs) ranged from 0.2 to 100 μg·kg-1. This method has been applied to the determination of real samples.

  • Xiao-ming ZHANG, He-yang LI, Zhe DENG, Nai-song QI, Xi WU, Yi LI, Lü-yin WANG, Ping LÜ, Cheng-gang LIANG, Jing LI
    Acta Pharmaceutica Sinica. 2025, 60(3): 784-790.

    To explore the standardization of the in vitro Nb2-11 cell proliferation bioassay for recombinant human growth hormone (rhGH), we first tested the biological activity of 2 batches of rhGH drug substances, 3 batches of rhGH for injection, and 24 batches of rhGH injections, based on which we proposed the experimental effective criteria. Furthermore, we conducted methodological validation in accordance with General Rule 9401 of the 2020 edition of the Pharmacopoeia of the People's Republic of China. Subsequently, the inter-laboratory consistency, intra-laboratory and inter-laboratory precision of seven labs were studied by determining the in vitro bioactivity of six batches of rhGH products and two batches of rhGH drug substances from four different manufacturers using this method. The consistency of the in vitro and in vivo bioassays was assessed by evaluating 28 batches of rhGH drug substances with both methods. Finally, multiple batches of rhGH samples with different expiration dates were tested to determine the standard limits of the bioassay. The results of this collaborative study indicate that the Nb2-11 cell bioassay exhibits good intra- and inter-laboratory reproducibility, with a 100% pass rate for the experimental effective criteria. The Nb2-11 cell bioassay had high consistency with in vivo animal bioassay. Animal experiments were approved by the Experimental Animal Welfare Ethics Committee of China National Institute of Food and Drug Control (approval number: NIFDC (Fu) No. 2024 (B) 004). This method is applicable to rhGH drug substances and products from different manufacturers. Collectively, the Nb2-11 cell bioassay can be used as a standardized method for determining the biological activity of rhGH products, replacing in vivo animal methods for quality control and release testing.

  • Xiao-shuang XU, Da-wei ZHANG
    Acta Pharmaceutica Sinica. 2025, 60(3): 817-824.

    The HIV-1 capsid protein (CA) is an effective target for antiviral drug discovery. Targeting the capsid assembly inhibitor peptide (CAI) binding pocket in the C-terminal domain of HIV-1 CA (CA CTD) can be used to screen for CA protein inhibitors. In this study, we found that the small molecule suramin targets HIV-1 CA by binding to this pocket, with an IC50 value of 2.1 μmol·L-1 for inhibiting the CA CTD-CAI interaction, based on homogeneous time-resolved fluorescence (HTRF) technology. Bio-layer interferometry (BLI) experiments demonstrated that suramin binds directly to CA, with a binding affinity to CA hexamer (KD = 248 nmol·L-1) higher than to CA monomer (KD = 227 μmol·L-1). In addition, in vitro CA protein assembly assays showed that suramin promotes disordered multimerization of CA protein. Binding model analysis revealed that suramin binds to the interface between adjacent CA monomers in the CA hexamer through the N57, Q63, Q67 and Y169 residues, thereby enhancing CA multimerization. In summary, suramin is a CA protein inhibitor that targets the CA hexamer and can serve as a starting point for the discovery of new CA inhibitors.

  • Zheng WANG, Chun-ze ZHANG
    Acta Pharmaceutica Sinica. 2025, 60(3): 559-572.

    Colorectal cancer is a major cancer threatening the life and health of people worldwide. With the transformation of modern medical models, treatment strategies represented by traditional Chinese medicine (TCM) with multiple targets have become a new research direction in the treatment of colorectal cancer. In the study of TCM, in addition to deconstructing the components and targets of TCM based on reductionism, more attention should be paid to the holistic concept in the basic theories of TCM, analyzing and understanding the mechanism of action of TCM treatment from a holistic perspective. TCM compound prescriptions, as a collection of single herbs, are composed of various monomers. Viewing TCM from different levels and considering different herbs and monomers as a whole helps us better understand TCM. At the same time, TCM has the characteristic of multiple targets. In addition to directly acting on tumor cells themselves, it can also affect the intestinal flora to improve the tumor microenvironment, treating tumors in an all-round and multi-dimensional way, regulating the physical functions of tumor patients from a holistic perspective, and comprehensively improving the health status of the individual. This review aims to systematically elaborate on the efficacy and multi-target mechanism of TCM in the treatment of colorectal cancer from three levels: TCM compound prescriptions, single herbs, and TCM monomers, based on clinical trials and preclinical research results. Meanwhile, this article will combine systems biology with the holistic view of TCM to conduct an in-depth analysis of related research on TCM treatment of colorectal cancer.

  • Miao-miao LUO, Hong-zhan XU, Jing HE, Xiao-jing LIU, Zi-xin ZHAO, Yun-yun JIANG, Ting-ting ZHOU
    Acta Pharmaceutica Sinica. 2025, 60(3): 655-666.

    In the study, we employed an untargeted metabolomic approach in conjunction with 16S rRNA high-throughput sequencing to identify potential antidepressant active effectors mediated by gut-flora among geniposides. Firstly, the rat depressed model was constructed using chronic unpredictable mild stress stimulation (CUMS) combined with orphaned model. Then the cecal contents of the rats were analyzed by untargeted metabolomics using ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF-MS) in order to identify differential metabolites. The intestinal genera exhibiting significant differences in the cecal contents were identified through 16S rRNA high-throughput sequencing, and correlation analysis was subsequently conducted between the differential metabolites and the intestinal genera. The comparison of the metabolic profiles between the normal control group, the depression model group, and the geniposide treatment group revealed that 147 metabolites were down-regulated and 381 metabolites were up-regulated in the model group compared with the normal group. Furthermore, 212 metabolites were up-regulated and 288 metabolites were down-regulated in the geniposide treatment group compared with the model group. Subsequently, the combination of the screening conditions of FC (fold change) > 2, P < 0.05 and VIP (variable importance in the projection) > 1, secondary mapping and database comparison led to the identification of 55 metabolites with significant differences among the three groups. The results of the metabolic pathway enrichment analysis indicated that the identified differential metabolites were primarily involved in five metabolic pathways, namely tryptophan metabolism, arginine biosynthesis, phenylalanine biosynthesis with tyrosine and tryptophan, phenylalanine metabolism, and arginine metabolism with proline. The 16S rRNA sequencing results further indicated that Gardenia jasminoides extract may exert its antidepressant effects, thereby providing a new basis for the study of the gut-brain axis in the therapeutic strategy of depression. All animal experiments were conducted with the approval of the Biomedical Research Ethics Committee of the Naval Medical University.

  • Qiu-yi QIN, Lin LI, Yi-hai WANG, Jing-wen XU, Xiang-jiu HE
    Acta Pharmaceutica Sinica. 2025, 60(3): 595-605.

    Arjunic acid (AR), a main bioactive triterpenoid isolated from acorns, has been reported to exert pronounced anti-inflammatory activities. However, its anti-inflammatory mechanisms have not been elucidated. In this study, the model of lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells were established to investigate the anti-inflammatory activity of AR. The potent targets and signaling pathway of AR for the treatment of inflammation-related disease were predicted based on network pharmacology. Furthermore, the expression of pro-inflammatory cytokines and mediators was determined by Griess assay, enzyme-linked immunosorbent assay (ELISA), qRT-PCR, and Western blot. The protein expression of NF-κB, MAPK, Nrf2/HO-1, PI3K/Akt/mTOR, and autophagy signaling pathways were gauged by Western blot. As the result, in the inflammatory model of LPS-induced RAW264.7 cells, AR could significantly inhibit the expression of pro-inflammatory cytokines and mediators, suppress the phosphorylation and translocation of NF-κB, and downregulate the phosphorylation of JNK/ERK signaling pathways. AR also inhibited ROS production and activated the Nrf2/HO-1 signaling pathway by degrading Keap1. Furthermore, AR activated autophagic flux by inhibiting the PI3K/Akt/mTOR signaling pathway. Collectively, AR was a potential natural product for the treatment of inflammation-related diseases.

  • Yi-jun LIU, Hong-juan WANG, Jing-bin ZHANG, Huan CHEN, Hong-wei HOU, Qing-yuan HU
    Acta Pharmaceutica Sinica. 2025, 60(3): 721-730.

    Plant-derived extracellular vesicles (PDEVs) are lipid bilayer-structured nanovesicles secreted by plant cells, recognized as excellent drug carriers due to their high stability, safety, and modifiability. As an emerging drug delivery system, PDEVs are gaining increasing attention. This review systematically summarizes the latest research progress on the preparation, characterization, engineering transformation, drug loading methods, and the applications and advantages of PDEVs as drug carriers. Finally, the future development directions of PDEVs in drug delivery are discussed.